ADMIRAL TRIAL

The ADMIRAL Trial Is a Phase 3 Study of the Only FDA-Approved Treatment in Relapsed or Refractory FLT3m+ AML1-3

XOSPATA—an oral monotherapy FLT3-ITD and -TKD inhibitor—was evaluated in a Phase 3, open-label, multicenter, randomized clinical trial compared with a prespecified salvage chemotherapy in adult patients with relapsed or refractory FLT3m+ AML.1,2

ADMIRAL study design1,2


Group 10
Group 11
  • Randomization was stratified by patient response to first-line AML treatment and prespecified chemotherapy.§ Prespecified chemotherapy regimens included1:
    • High-intensity combination regimens MEC|| and FLAG-IDA
    • Low-intensity regimens LDAC# and AZA**
  • The efficacy of XOSPATA was based on an interim analysis and a final analysis1:
    • CR/CRh was evaluated in an interim analysis in the XOSPATA arm only (n=138) and was summarized in the final analysis for both treatment groups1,2
    • The final analysis evaluated OS with XOSPATA vs salvage chemotherapy1

*XOSPATA was given orally at a starting dose of 120 mg daily until unacceptable toxicity or lack of clinical benefit.1

Patients in the ADMIRAL trial were eligible for HSCT. Patients who went on to receive transplant during the study had achieved a response in either treatment arm that allowed them to undergo HSCT based on each institution's assessment, and had a suitable donor identified. Treatment with XOSPATA was stopped prior to starting the conditioning regimen for HSCT and could be resumed after transplant in patients meeting appropriate study protocol criteria.2

Only responses prior to HSCT were included in the CR/CRh rate reported in the XOSPATA Prescribing Information.1

§Prior AML chemotherapy regimens included standard-dose cytarabine + idarubicin (39%); high-dose cytarabine (27%); standard-dose cytarabine + daunorubicin (26%); azacitidine (7%); decitabine (5%); high-dose cytarabine + daunorubicin (4%); low-dose cytarabine (4%); high-dose cytarabine + idarubicin (3%); standard-dose cytarabine + mitoxantrone (3%); and standard-dose cytarabine + daunorubicin + cladribine (1%); as well as other regimens (44%).2

||MEC: mitoxantrone 8 mg/m2, etoposide 100 mg/m2, and cytarabine 1000 mg/m2 once daily by IV infusion Days 1 to 5.1

FLAG-IDA: granulocyte colony-stimulating factor 300 mcg/m2 once daily by SC injection Days 1 to 5, fludarabine 30 mg/m2 once daily by IV infusion Days 2 through 6, cytarabine 2000 mg/m2 once daily by IV infusion Days 2 through 6, idarubicin 10 mg/m2 once daily by IV infusion Days 2 through 4.1

#LDAC: cytarabine 20 mg twice daily by SC injection or IV infusion for 10 days.1

**AZA: azacitidine 75 mg/m2 once daily by SC injection or IV infusion for 7 days.1

Key Eligibility Criteria4††

  • Adult patients with primary AML or AML secondary to myelodysplastic syndrome
  • Positive for FLT3 mutations (FLT3-ITD, FLT3-TKD-D835, or FLT3-TKD-I836) as determined by the central lab
  • Refractory to, or relapsed after, first-line AML therapy (with or without HSCT)

Exclusion Criteria4††

  • Patients in second or later hematologic relapse or having received salvage therapy for refractory disease
  • Patients with long QT syndrome at screening
  • Patients with hypokalemia and hypomagnesemia at screening (defined as values below LLN)

Patients Permitted

  • Patients with prior HSCT (n=74/371)5
  • Patients who were transfusion dependent (n=294/371)1
  • Patients previously treated with midostaurin or sorafenib (n=45/371)2,4

††Does not include all patient inclusion and exclusion criteria for the ADMIRAL trial.4

During the ADMIRAL trial, patients who achieved a response in either treatment arm that allowed them to undergo HSCT‡‡ based on each institution's assessment—and who had a suitable donor identified—went on to receive transplant during the study.

26%

of patients in the XOSPATA arm received HSCT (95% CI: 20.2, 31.4; n=63/247)

15%

of patients in the salvage chemotherapy arm received HSCT (95% CI: 9.5, 22.9; n=19/124)

‡‡Treatment with XOSPATA was stopped prior to starting the conditioning regimen for HSCT. XOSPATA treatment could be resumed after transplant in patients who were between 30 and 90 days post-HSCT, had successful engraftment with ANC ≥500/mm3 and platelets ≥20,000/mm3 without transfusions, did not have Grade ≥2 acute graft-vs-host disease, and were in composite complete remission (CRc).2

Table of baseline patient characteristics in the ADMIRAL Trial Table of baseline patient characteristics in the ADMIRAL Trial

§§The remaining 5 patients were negative by the diagnostic test.2

||||One patient in the comparator salvage chemotherapy arm had refractory relapse AML at baseline.1

¶¶The remaining 58 patients included those with cytogenetic risk status that cannot be categorized as intermediate, unfavorable, or favorable.2

##Patients were defined as transfusion dependent at baseline if they were dosed and received any RBC or platelet transfusions within the 56-day baseline period.1

AML=acute myeloid leukemia; ANC=absolute neutrophil count; CI=confidence interval; CR=complete remission; CRh=complete remission with partial hematologic recovery; FLT3=FMS-like tyrosine kinase 3; HSCT=hematopoietic stem cell transplant; ITD=internal tandem duplication; IV=intravenous; LDAC=low-dose cytarabine; LLN=lower limit of normal; m+=mutation-positive; OS=overall survival; QT=cardiac ventricular repolarization; RBC=red blood cell; SC=subcutaneous; TKD=tyrosine kinase domain.

References: 1. XOSPATA [package insert]. Northbrook, IL: Astellas Pharma US, Inc. 2. Astellas. XOSPATA. Data on File. 3. Ballesta-López O, Solana-Altabella A, Megías-Vericat JE, Martínez-Cuadrón D, Montesinos P. Gilteritinib use in the treatment of relapsed or refractory acute myeloid leukemia with a FLT3 mutation. Future Oncol (Epub) 09-25-2020. 4. ClinicalTrials.gov. A study of ASP2215 versus salvage chemotherapy in patients with relapsed or refractory acute myeloid leukemia (AML) with FMS-like tyrosine kinase (FLT3) mutation (01-19-2021). https://clinicaltrials.gov/ct2/show/NCT02421939. Accessed 02-01-2021. 5. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med 2019;381(18):1728-40.